PROJECT SUMMARY Iron deficiency (ID) affects an estimated 9 to 16% of adolescent girls in the United States and disproportionately affects African American girls. ID, with and without anemia, is associated with decreased cognitive function, diminished exercise capacity, and increased fatigue. Unrecognized ID can progress to complications of severe anemia. Despite readily available therapy with oral iron, there are no universal screening recommendations or evidence-based risk prediction tools to identify those girls at highest risk for its development. Early identification of at-risk girls would allow for well-designed, long-term, controlled studies that evaluate the effects of screening for and early treatment of ID on important health outcomes. The research aims of this project are to: 1) determine the prevalence of, timing of, and risk factors for ID in a large, biracial cohort of adolescent girls; and 2) identify novel biomarkers of ID through global serum profiling by metabolomics. To achieve this goal, we will utilize existing clinical data and specimens from the National Heart Lung and Blood Institute (NHLBI) Growth and Health Study (NGHS), a longitudinal study of obesity risk factors in African American and Caucasian girls followed annually from age 9-10 years to 18-19 years. We will assay serum samples drawn at serial time points (Years 1, 3, 5, 7, and 10) from NGHS subjects for whom at least 4 samples are available (n=693) over the 10-year period. We will determine ID status using both traditional and novel iron parameters, including serum ferritin and soluble transferrin receptor 1 (sTfR1) to determine the prevalence and timing of ID and assess clinical risk factors that are predictive of the ID development. We will perform unbiased profiling of metabolites in 40 samples to characterize metabolites that are altered in ID versus non-ID subjects and compare candidate metabolites to standard iron parameters to find those that may be used as predictive markers of ID in minority and/or obese populations. Our research team?s experience in epidemiologic and interventional studies in the field of ID, methodologic experience with the use of large datasets, and track record of performing large-scale bioassays, well-positions us to achieve our objectives. The results from this study will inform both the development of a risk prediction tool and evidenced-based screening recommendations for ID in adolescent girls. Identifying metabolites associated with ID will substantiate the prognostic value of candidate metabolites as biomarkers of ID compared to standard iron parameters. Overall, this work is required to provide the preliminary data that justifies a future R01 application to fully assess the benefits of ID screening, treatment initiation, and follow-up. The results will directly address the U.S. Department of Health and Human Services? Healthy People objective of reducing ID in adolescent girls and young women.